Soluble Guanylate Cyclase Stimulator, BAY41-8543: A Promising Approach for the Treatment of Chronic Heart Failure Caused by Pressure and Volume Overload
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F25%3A00085502" target="_blank" >RIV/00023001:_____/25:00085502 - isvavai.cz</a>
Result on the web
<a href="https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1002/prp2.70087" target="_blank" >https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1002/prp2.70087</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/prp2.70087" target="_blank" >10.1002/prp2.70087</a>
Alternative languages
Result language
angličtina
Original language name
Soluble Guanylate Cyclase Stimulator, BAY41-8543: A Promising Approach for the Treatment of Chronic Heart Failure Caused by Pressure and Volume Overload
Original language description
Heart failure (HF) is a leading cause of morbidity and mortality, often driven by prolonged exposure to pathological stimuli such as pressure and volume overload. These factors contribute to excessive oxidative stress, adverse cardiac remodeling, and dysregulation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway. Given the urgent need for effective treatments, this study investigated the potential of sGC stimulators to mitigate HF progression. We utilized male hypertensive Ren-2 transgenic (TGR) rats and a volume-overload HF model induced by an aortocaval fistula (ACF). Rats received the sGC stimulator BAY 41-8543 (3 mg/kg/day) for 30 weeks, while normotensive Hannover Sprague-Dawley rats served as controls. At the study endpoint (40 weeks of age), left ventricular tissue was analyzed using mass spectrometry, Western blotting, and histological assessment. TGR rats treated with sGC stimulators exhibited a significant increase in key antioxidant proteins (SOD1, CH10, ACSF2, NDUS1, DHE3, GSTM2, and PCCA), suggesting enhanced resistance to oxidative stress. However, sGC stimulator treatment also upregulated extracellular matrix remodeling markers (MMP-2, TGF-beta, and SMAD2/3), which are typically associated with fibrosis. Despite this, Masson's trichrome staining revealed reduced collagen deposition in both TGR and TGR-ACF rats receiving sGC stimulators. Notably, all untreated TGR-ACF rats succumbed before the study endpoint, preventing direct assessment of sGC stimulator effects in advanced HF. These findings highlight the therapeutic potential of sGC stimulators in HF, particularly through their antioxidant effects. However, their concurrent influence on fibrosis warrants further investigation to optimize treatment strategies.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Pharmacology Research & Perspectives
ISSN
2052-1707
e-ISSN
2052-1707
Volume of the periodical
13
Issue of the periodical within the volume
2
Country of publishing house
GB - UNITED KINGDOM
Number of pages
15
Pages from-to
"art. no. e70087"
UT code for WoS article
001456244600001
EID of the result in the Scopus database
2-s2.0-105002006479